1. Field of the Invention
The invention relates to immunology and more particularly to phagemids.
2. Brief Description of Related Art
Experimental systems have been developed which mimic or directly use the broad repertoire of structures generated in natural production of antibodies. This has been extended by the introduction of additional combinatorial components by mixing of light and heavy immunoglobulin chains and by taking naive repertoires (e. g. IgM) which contain also variants which would normally have been eliminated since they cross-react with endogenes antigenes.
Further, a directed evolution of a protein has been described by selecting mutant neutrophil elastase inhibitors displayed on M13 fusion phages Roberts B. L., Markland W., Ley A. C., Kent R. B., White D. W. Guterman S. K. and Ladner R. C. (1992) Directed evolution of a protein: selection of potent neutrophil elastase inhibitors displayed on M13 fusion phage. Proc. Natl. Acad. Sci. USA 89, 2429-2433. The stability of this known system is, however, critical. An object of the present invention is to select ligands directed towards compact target sites which must be regarded as a complementary alternative to known systems which use larger molecules in which the variable regions are spread over larger areas.